Rolling Ultrasharp Microneedle Spheres Enable Topical Delivery of Biologics Through the Skin.

Topical drug delivery offers a localized and patient-friendly method for treating skin diseases and subcutaneous lesions. However, the outermost skin barrier - the stratum corneum (SC) - hinders the delivery of large molecules such as biopharmaceuticals. This study introduces rolling ultraminiaturized microneedle spheres (RUMS) as a novel solution that enables topical delivery of messenger RNA (mRNA) without the need for chemical enhancers or techniques like electroporation, iontophoresis, or microneedle patches. RUMS are engineered spherical microparticles that gently roll over the skin, creating numerous micropores while minimizing tissue damage. In ex vivo porcine skin experiments, 25 RUMS generated approximately 4,500 pores within 10 seconds, achieving penetration depths of around 20 micrometers and increasing skin permeability by up to 100-fold. In vivo studies in mice showed that combining RUMS with topical doxycycline led to a ~50% tumor size reduction within two weeks and full recovery by four weeks. In contrast, doxycycline or RUMS alone offered limited therapeutic benefit. Rapid skin healing was observed due to the small pore size. Additionally, topical delivery of lipid nanoparticle-encapsulated luciferase (luc)-encoding mRNA was successfully demonstrated in mice. Overall, use of RUMS presents a simple, painless, and potentially well-tolerated technique for enabling transdermal topical delivery of biologics.